Applicants herein are the inventors of U.S. Pat. No. 5,070,874, issued Dec. 10, 1991, for "Non-invasive Determination of Glucose Concentration in Body of Patient."
This invention relates to the determination of the concentration of analytes in the body of a mammal, and in particular to the determination of the concentration of glucose in the blood of a patient who is suspected of suffering from diabetes or to control the treatment or medication of patients who already suffer from diabetes. It has particular relationship to such determination without drawing blood from the patient, i.e., by a non-invasive process and by non-invasive means.
There is widespread demand for non-invasive determination of glucose in patients. In the United States there are approximately ten million diabetics. Two million of these are Type 1 Diabetics, whose pancreas secretes no insulin; and eight million of these are Type 2 Diabetics, whose pancreas secretes insufficient insulin or secretes it too late. Most of the Type 2 Diabetics can be controlled with proper diet and weight control. Some of the Type 2 Diabetics and all of the Type 1 Diabetics require one or more shots of insulin per day. Insulin controls the body's utilization of glucose or sugar in the blood and, in the correct concentrations, prevents hyperglycemia (excess glucose) which, if left uncorrected, can lead to ketosis, coma and death. Glucose determination is also indispensable for sufferers from hypoglycemia who must ingest glucose containing fluids, such as orange juice, if the glucose in their blood decreases to a low level.
Hyperglycemia in the diabetic is strongly suspected of being responsible for the long-term effects of diabetes which include heart disease, arteriosclerosis, blindness, stroke, hypertension, kidney failure, and premature death. Severe hypoglycemia has similar drastic consequences. In a normal person, the blood glucose level may vary between 60 and 130 milligrams per deciliter, a variance exceeding 100%; whereas, in a diabetic, the levels may vary from time to time from 40 to 500 milligrams per deciliter, a variance of 1150% for hyperglycemia. For hypoglycemia, 60 milligrams per deciliter indicates that treatment is necessary; the glucose may reach a dangerous level of 20 milligrams per deciliter. These large swings of glucose levels must be avoided to prevent the symptoms and complications of the disease. To avoid the swings, the diabetic must be able to conveniently monitor his blood glucose level, and then vary his caloric intake, diet and insulin to control the level. For effective control, frequent blood glucose monitoring is necessary.
The only practicable, reliable method currently available for monitoring blood glucose is by means of blood sampling. The diabetic pricks his epidermis with a needle or lance, usually in the finger, draws a drop of blood, and absorbs the blood on a chemically treated strip of paper. He can then read the glucose level by placing the strip in a glucometer (a spectrophotometer which reads glucose concentrations); or he can compare the color change of the strip with a calibrated color chart. The direct reading instruments are more accurate. Other methods include measuring the electrical resistance of the strip with a glucometer which is an ohmmeter calibrated in milligrams per deciliter. For effective control, some diabetics must utilize a finger prick four or more times a day.
It is desirable to dispense with the drawing and analyzing of blood and it is an object of this invention to achieve this purpose, providing for effective non-invasive determination of analyte concentration in the body of a mammal, and in particular glucose concentration in a patient suspected to suffer from, or already suffering from, diabetes.
European Publication 0 160 768, dated Nov. 13, 1985, to Clause Dahne and Daniel Cross, discloses one prior art technique for the non-invasive determination of glucose concentration. In Dahne, a beam of radiation in selected bands, 1575, 1765, 2100 and 2270.+-.15 nanometers is impinged on a portion of the patient's body, penetrating into the portion, and the radiation resulting from the reaction within the body on the incident radiation is analyzed photometrically for the presence quantitatively of glucose. The resulting radiation which is analyzed may be scattered radiation or the transmitted radiation which, in effect, is the incident radiation less the predominant fraction of the scattered radiation and the radiation absorbed by the portion of the body.
Dahne suffers from the disadvantage that its process lacks the precision demanded for the effective monitoring of glucose concentration. The range of concentration over which the glucose is in practice monitored for effective control of the patient is between 40 and 500 milligrams per deciliter, but even lower concentrations may be encountered in hyperglycemia or hypoglycemia. A concentration appreciably greater than 120 milligrams per deciliter indicates a diabetic condition and treatment by diet or insulin. In the actual practice of Dahne's process, the highest concentration of glucose which was measured was one molar (1M) and the lowest concentration of glucose which was measured was 0.05 molar (page 18). The chemical formula for glucose is C.sub.6 H.sub.12 O.sub.6. In a 1M solution of glucose, there are 180.16 grams per liter or 18,000 milligrams per deciliter. In 0.05 mole, there are 0.9 grams or 900 milligrams per deciliter. This is far out of the range of glucose concentrations which must be measured for effective control and, indeed, out of the range which is compatible with life. There is no evidence in Dahne that its process is more effective than is indicated by its tests.
It is accordingly an object of this invention to overcome the disadvantages and drawbacks of the prior art and to provide for the precise effective non-invasive determination of the concentration of blood analytes in a mammal, and particularly glucose in a human patient, taking into consideration the concentrations actually involved in such determination.